Clinical Trial Results:
An Open-Label Study of Brentuximab Vedotin+Adriamycin, Vinblastine, and Dacarbazine in Pediatric Patients With Advanced Stage Newly Diagnosed Hodgkin Lymphoma
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Summary
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EudraCT number |
2015-004112-38 |
Trial protocol |
IT ES |
Global end of trial date |
24 Sep 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Apr 2022
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First version publication date |
08 Apr 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
C25004
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02979522 | ||
WHO universal trial number (UTN) |
U1111-1171-0984 | ||
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Sponsors
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Sponsor organisation name |
Takeda
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Sponsor organisation address |
95 Hayden Avenue, Lexington, United States, MA 02421
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Public contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Scientific contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000980-PIP01-10 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Sep 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Sep 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The purpose of this study is to assess the safety, tolerability, and anti-tumor activity, as well as confirm the recommended dose of brentuximab vedotin (ADCETRIS) in combination with a multiagent chemotherapy regimen, doxorubicin (Adriamycin), vinblastine, and dacarbazine, in pediatric participants with advanced stage newly diagnosed classical CD30+ Hodgkin Lymphoma (HL).
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Protection of trial subjects |
All study participants were required to read and sign an Informed Consent Form (ICF).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Sep 2017
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
10 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 12
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Country: Number of subjects enrolled |
Brazil: 30
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Country: Number of subjects enrolled |
Italy: 15
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Country: Number of subjects enrolled |
Japan: 2
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Worldwide total number of subjects |
59
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EEA total number of subjects |
15
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
11
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Adolescents (12-17 years) |
48
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants with advanced stage newly diagnosed, classical CD30+ Hodgkin Lymphoma (HL) took part in the study at 14 investigative sites in the United States, Italy, Brazil and Japan from 06 September 2017 to 24 September 2021. | |||||||||
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Pre-assignment
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Screening details |
Participants with advanced stage newly diagnosed, classical CD30+ HL were received brentuximab vedotin in combination with doxorubicin, vinblastine, and dacarbazine(A+AVD). Data for Phase 2 endpoints is reported for Phase 2 participants only and all participants treated in Phase 1 with additional enrolled participants in Phase 2. | |||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD | |||||||||
Arm description |
Brentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Brentuximab vedotin
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Investigational medicinal product code |
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Other name |
Adcetris
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravascular use
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Dosage and administration details |
Brentuximab vedotin 48 mg/m^2 infusion once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
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Investigational medicinal product name |
Vinblastine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Vinblastine 6 mg/m^2 infusion once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
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Investigational medicinal product name |
Dacarbazine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Dacarbazine 375 mg/m^2 infusion once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
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Investigational medicinal product name |
Doxorubicin
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Investigational medicinal product code |
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Other name |
Adriamycin
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Doxorubicin 25 mg/m^2 infusion once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
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Arm title
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Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | |||||||||
Arm description |
Brentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Brentuximab vedotin
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Investigational medicinal product code |
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Other name |
Adcetris
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravascular use
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Dosage and administration details |
Brentuximab vedotin 48 mg/m^2 infusion once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
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Investigational medicinal product name |
Doxorubicin
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Investigational medicinal product code |
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Other name |
Adriamycin
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Doxorubicin 25 mg/m^2 infusion once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
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Investigational medicinal product name |
Vinblastine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Vinblastine 6 mg/m^2 infusion once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
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Investigational medicinal product name |
Dacarbazine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Dacarbazine 375 mg/m^2 infusion once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
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Baseline characteristics reporting groups
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Reporting group title |
Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD
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Reporting group description |
Brentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD
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Reporting group description |
Brentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Phase 1+ 2: Brentuximab Vedotin 48 mg/m^2 + AVD
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Brentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
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End points reporting groups
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Reporting group title |
Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD
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Reporting group description |
Brentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles. | ||
Reporting group title |
Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD
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Reporting group description |
Brentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles. | ||
Subject analysis set title |
Phase 1+ 2: Brentuximab Vedotin 48 mg/m^2 + AVD
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Brentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
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End point title |
Phase 1: Recommended Dose of Brentuximab Vedotin in Combination With Doxorubicin, Vinblastine, and Dacarbazine in a Pediatric Population [1] [2] | ||||||||
End point description |
The recommended dose was determined after considering all safety data in phase 1 and assessing for dose limiting toxicities (DLTs) which are defined as the dose range at which less than or equal to (<=) 1 of 6 evaluable participants experience DLT within the defined observation period (Cycle 1 + 28 days). This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. The DLT-evaluable population included participants who had received at least 1 dose of study drug therapy and experienced a DLT or no DLT during the DLT observation period. Participants who received granulocyte colony stimulating factor (G-CSF) during the DLT observation period were excluded from the DLT-Evaluable Population.
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End point type |
Primary
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End point timeframe |
From the first dose (Cycle 1) up to Day 56 (Cycle length=28 days)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analyses was available for this endpoint. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Phase 1: Percentage of Participants Who Experienced Adverse Events (AEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy [3] [4] | ||||||||
End point description |
AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. The safety population included participants who had received at least 1 dose of any study drug (A+AVD regimen).
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End point type |
Primary
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End point timeframe |
From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analyses was available for this endpoint. [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Phase 1: Percentage of Participants Who Experienced Serious Adverse Events (SAEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy [5] [6] | ||||||||
End point description |
AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in death, Is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, Is a congenital anomaly/birth defect, Is a medically important event. The safety population included participants who had received at least 1 dose of any study drug (A+AVD regimen).
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End point type |
Primary
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End point timeframe |
From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analyses was available for this endpoint. [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Phase 2: Percentage of Participants Who Achieved a Complete Remission (CR) Per Independent Review Facility (IRF) Assessment Per International Working Group (IWG) Criteria at End of Treatment (EOT) Visit [7] [8] | ||||||||||||
End point description |
CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in the statistical analysis plan (SAP) , data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
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End point type |
Primary
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End point timeframe |
At end of treatment (EOT) visit 30 days after the last dose of study drug (at Month 7)
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analyses was available for this endpoint. [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Phase 2: Percentage of Participants Whose Disease Was Positron Emission Tomography (PET) Negative After 2 Cycles of Protocol Therapy Per IRF Assessment [9] [10] | ||||||||||||
End point description |
The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET negative after Cycle 2 was defined as an IRF Deauville score of (1 or 2 or 3). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
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End point type |
Primary
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End point timeframe |
From first dose of study drug up to Cycle 2 Day 25 (Each Cycle length=28 days)
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| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analyses was available for this endpoint. [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Phase 2: Percentage of Participants Who Achieved a Partial Remission (PR) Per IRF Assessment Per IWG Criteria at EOT Visit [11] [12] | ||||||||||||
End point description |
PR was defined as regression of measurable disease and no new sites as assessed by IRF as per IWG criteria. Percentage of participants in the response-evaluable population who achieved a partial response based on the IRF assessment at the EOT visit based on the IWG criteria are reported. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
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End point type |
Primary
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End point timeframe |
At EOT visit 30 days after the last dose of study drug (at Month 7)
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| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analyses was available for this endpoint. [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Phase 2: Percentage of Participants Who Achieved an Overall Response Rate (ORR) Per IRF Assessment Per IWG Criteria at EOT Visit [13] [14] | ||||||||||||
End point description |
Overall response rate was defined as the percentage of participants with CR or PR as assessed by IRF using IWG criteria. CR was defined as the disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new diseases. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
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End point type |
Primary
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End point timeframe |
At EOT visit 30 days after the last dose of study drug (at Month 7)
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| Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analyses was available for this endpoint. [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Phase 2: Percentage of Participants Who Were Able to Complete 6 Cycles of Protocol Therapy at the Recommended Dose [15] [16] | ||||||||||||
End point description |
This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. The safety population included participants who had received at least 1 dose of any study drug (A+AVD regimen).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
From first dose of study drug up to Cycle 6 (Each Cycle length=28 days)
|
||||||||||||
| Notes [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analyses was available for this endpoint. [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||
End point title |
Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin Total Conjugated and Therapeutic Antibody (TAb) [17] [18] | ||||||||||||||||||||||||
End point description |
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter. 'n'= Number analysed is number of participants with data available for analysis at the given time point.
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||||||||||||||
| Notes [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analyses was available for this endpoint. [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| Notes [19] - n= 7,6,8,7,7,6,6,6 |
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||
End point title |
Phase 1: Mean Maximum Observed Plasma Concentration (Cmax) of Monomethyl Auristatin E (MMAE) [20] | ||||||||||||||||
End point description |
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter. 'n'= Number analyzed is number of participants with data available for analysis at the given time point.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||||||
| Notes [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
|||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb [21] | ||||||||||||||||||||||||
End point description |
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. 'n'= Number analyzed is number of participants with data available for analysis at the given time point.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||||||||||||||
| Notes [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| Notes [22] - n=7,6,7,6,7,6,6,6 |
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||
End point title |
Phase 1: Mean Area Under the Plasma Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of MMAE [23] | ||||||||||||||||
End point description |
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. 'n'= Number analyzed is number of participants with data available for analysis at the given time point.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||||||
| Notes [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
|||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||
End point title |
Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin and TAb in Serum [24] | ||||||||||||||||||||
End point description |
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter. 'n'= Number analyzed is number of participants with data available for analysis at the given time point.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||||||||||
| Notes [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
|||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||
End point title |
Phase 1: Median Time to Reach Cmax (Tmax) of MMAE in Plasma [25] | ||||||||||||||||
End point description |
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter. 'n'= Number analyzed is number of participants with data available for analysis at the given time point.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||||||
| Notes [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
|||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||
End point title |
Phase 1: Percentage of Participants Who Achieved a CR Per IRF Assessment Per IWG Criteria at EOT Visit [26] | ||||||||
End point description |
CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm. Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
At EOT visit 30 days after the last dose of study drug (at Month 7)
|
||||||||
| Notes [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Phase 1: Percentage of Participants Who Achieved a PR Per IRF Assessment Per IWG Criteria at EOT Visit [27] | ||||||||
End point description |
PR was defined as regression of measurable disease and no new diseases as per IWG Criteria based on IRF. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm. Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
At EOT visit 30 days after the last dose of study drug (at Month 7)
|
||||||||
| Notes [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Phase 1: Percentage of Participants Who Achieved an ORR Per IRF Assessment Per IWG Criteria at EOT Visit [28] | ||||||||
End point description |
Overall response rate was defined as the percentage of participants with CR or PR as assessed by an IRF using IWG Revised Response Criteria. CR was defined as the disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm. Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
At EOT visit 30 days after the last dose of study drug (at Month 7)
|
||||||||
| Notes [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Phase 1: Percentage of Participants Whose Disease Was PET Negative After 2 Cycles of Protocol Therapy Per IRF Assessment [29] | ||||||||
End point description |
The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET negative after Cycle 2 was defined as an IRF Deauville score of (1 or 2 or 3). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm. Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From first dose of study drug up to Cycle 2 (Each Cycle length=28 days)
|
||||||||
| Notes [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Phase 1: Percentage of Participants Whose Disease Was PET Positive After 6 Cycles of Protocol Therapy Per IRF Assessment [30] | ||||||||
End point description |
The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET positive after Cycle 6 defined as an IRF Deauville score of (4 or 5). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm. This outcome measure was planned to be assessed only for participants treated in Phase 1 arm.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From first dose of study drug up to Cycle 6 (Each Cycle length=28 days)
|
||||||||
| Notes [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||
End point title |
Phase 1: Percentage of Participants Who Were Antitherapeutic Antibody (ATA) Positive, Persistently Positive or Transiently Positive, and Neutralizing Antitherapeutic Antibody (nATA) Positive [31] | ||||||||||||||
End point description |
ATA positive was defined as participants who have a positive ATA in any postbaseline sample. Transiently ATA positive was defined as participants who have positive ATA in 1 or 2 postbaseline samples. Persistently ATA positive was defined as participants who have positive ATA in more than 2 postbaseline timepoints. Transiently ATA positive was defined as participants who have positive ATA in 1 or 2 postbaseline samples. nATA positive was defined as participants who have at least one positive nATA in any postbaseline ATA positive sample. Here, percentage of participants who were transiently or persistently ATA positive are considered as ATA positive. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Immunogenicity population included participants who received at least 1 dose of study drug and had the baseline immunogenicity sample and at least 1 postbaseline immunogenicity sample assessment.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Up to 7 months
|
||||||||||||||
| Notes [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
|||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||
End point title |
Phase 2: Progression-free Survival (PFS) [32] | ||||||||||||
End point description |
PFS (IRF):time from 1st dose until disease progression per IRF/death due to any cause,whichever occurred first. Endpoint was planned to be assessed for all participant treated at recommended dose in Phase 2.As per SAP,Phase 2 data was summarized and reported in 2 arms:Phases 2 and Phase 1+ Phase 2. Median and 95% CI was not estimable as most of the participants were censored. The safety/efficacy population included participants who received at least 1 dose of any drug in the A+AVD regimen.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 24 months
|
||||||||||||
| Notes [32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Phase 2: Event-free Survival (EFS) [33] | ||||||||||||
End point description |
EFS:Time from first dose until any treatment failure:PD per IRF including progression events during follow-up period,failing to complete 6 cycles of treatment due to any reason or death due to any cause,whichever occurred first.EFS per IRF were censored on last adequate disease assessment date per IRF if none of above events occur during study. This w endpoint was planned to be assessed for all participants treated at recommended dose in Phase 2.As prespecified in SAP,data for Phase 2 was summarized and reported in two arms:Phase 2 and Phase 1 + Phase 2. The safety/efficacy population included participants who received at least 1 dose of any drug in the A+AVD regimen. For participants who do not have an objective PD and did not die at the last follow-up, EFS has been censored on the date of last adequate disease assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 24 months
|
||||||||||||
| Notes [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Phase 2: Overall Survival (OS) [34] | ||||||||||||
End point description |
Overall survival was defined as time from first dose until death. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive, including study closure. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. The safety/efficacy population included participants who received at least 1 dose of any drug in the A+AVD regimen. The safety/efficacy population included participants who received at least 1 dose of any drug in the A+AVD regimen.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 24 months
|
||||||||||||
| Notes [34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Phase 2: Duration of Response (DOR) [35] | ||||||||||||
End point description |
DOR per IRF in participants with a response (CR or PR per IRF) was defined as the time from start of the first objective tumor response (CR or PR per IRF) to the first subsequent PD or death due to any cause, whichever occurred first. This endpoint was planned to be assessed only for all participants treated at the recommended dose Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Response Evaluable Population=Participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment (assessments based on investigator assessments or assessments based on an independent review facility). For participants who do not have an objective PD and did not die at the last follow-up, DOR has been censored on the date of last adequate disease assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 24 months
|
||||||||||||
| Notes [35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Phase 2: Percentage of Participants Receiving Irradiation for HL Following Study Treatment [36] | ||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. The safety/efficacy population included participants who received at least 1 dose of any drug in the A+AVD regimen.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 24 months
|
||||||||||||
| Notes [36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Phase 2: Percentage of Participants Who Experienced AEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy [37] | ||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. The safety population included participants who had received at least 1 dose of any study drug (A+AVD regimen).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
|
||||||||||||
| Notes [37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Phase 2: Percentage of Participants Who Experienced SAEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy [38] | ||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. The safety population included participants who had received at least 1 dose of any study drug (A+AVD regimen).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
|
||||||||||||
| Notes [38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||||||||||||||
End point title |
Phase 2: Percentage of Participants Who Were ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive [39] | |||||||||||||||||||||
End point description |
ATA positive: participants who have a positive ATA in any postbaseline sample. Transiently ATA positive: participants who have positive ATA in 1 or 2 postbaseline samples. Persistently ATA positive was defined as participants who have positive ATA in more than 2 postbaseline timepoints. Transiently ATA positive: participants who have positive ATA in 1 or 2 postbaseline samples. nATA positive: participants who have at least one positive nATA in any postbaseline ATA positive sample. Here, percentage of participants who were transiently or persistently ATA positive are considered as ATA positive. This endpoint was planned to be assessed only for all participants treated at recommended dose in Phase 2. As prespecified in SAP, Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.Immunogenicity population: participants who received at least 1 dose of study drug and had the baseline immunogenicity sample and at least 1 postbaseline immunogenicity sample assessment.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
From first dose until 30 days after the last dose of study drug (up to 7 months)
|
|||||||||||||||||||||
| Notes [39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
||||||||||||||||||||||
|
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
End point title |
Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb [40] | ||||||||||||||||||||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. 'n'= Number analyzed is number of participants with data available for analysis at the given time point.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||||||||||||||||||||||||||
| Notes [40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
| Notes [41] - n=50, 34, 47, 25, 48, 34, 46, 25 [42] - n=57,40, 55, 32, 55, 40, 52, 31 |
|||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Phase 2: Mean Plasma Cmax of MMAE [43] | ||||||||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. 'n' = Number analyzed is number of participants with data available for analysis at the given time point.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||||||||||||||
| Notes [43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| Notes [44] - n=46,31,45,24 [45] - n=54,37,53,31 |
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
End point title |
Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb [46] | ||||||||||||||||||||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. 'n'= Number analyzed is number of participants with data available for analysis at the given time point.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||||||||||||||||||||||||||
| Notes [46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
| Notes [47] - n=50, 34, 47, 24, 48, 33, 46, 23 [48] - n=57,40, 54, 30, 55, 39, 52, 29 |
|||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Phase 2: Mean Plasma AUC0-15 of MMAE [49] | ||||||||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. 'n'= Number analyzed is number of participants with data available for analysis at the given time point.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||||||||||||||
| Notes [49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| Notes [50] - n=40, 28, 41, 16 [51] - n=47, 31, 48, 20 |
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
End point title |
Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum [52] | ||||||||||||||||||||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. 'n'= Number analyzed is number of participants with data available for analysis at the given time point.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||||||||||||||||||||||||||
| Notes [52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
| Notes [53] - n=50, 34, 47, 25, 48, 34, 46, 25 [54] - n=57,40, 55, 32, 55, 40, 52, 31 |
|||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Phase 2: Median Tmax of MMAE in Plasma [55] | ||||||||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. The PK population included participants with sufficient data to enable calculation of at least 1 PK parameter, with data available for analyses. "n"= Number analyzed is number of participants with data available for analysis at the given time point.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||||||||||||||
| Notes [55] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| Notes [56] - n=46,31,45,34 [57] - n=54,37,53,31 |
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||
End point title |
Phase 2: Percentage of Participants Who Experienced Peripheral Neuropathy, Regardless of Seriousness, From the First Dose of Protocol Therapy [58] | ||||||||||||
End point description |
Peripheral Neuropathy (PN) was defined by the peripheral neuropathy standardized MedDRA query (SMQ) broad search. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. The safety population included participants who received at least 1 dose of any drug in the A+AVD regimen.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 24 months
|
||||||||||||
| Notes [58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||
End point title |
Phase 2: Time to Onset and Resolution for All Peripheral Neuropathy Events [59] | ||||||||||||||||||
End point description |
Time to onset of first event was defined as time from first dose of study drug to onset of first treatment-emergent PN event. Time to resolution was calculated as the time from onset date to the date of resolution PN (SMQ) event. Participants with multiple resolved events were counted once at the longest time to resolution. Resolution was defined as an event outcome of resolved or resolved with sequelae. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. The safety population included participants who received at least 1 dose of any drug in the A+AVD regimen. Overall number analyzed signifies participants who had peripheral neuropathy were analyzed for this outcome measure, 'n' = number analyzed are participants with evaluable for the specific category.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Up to 24 months
|
||||||||||||||||||
| Notes [59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||||||||
|
|||||||||||||||||||
| Notes [60] - n=12,11 [61] - n=14,13 |
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Phase 2: Immune Reconstitution-Change From Baseline Immunoglobulin G Levels at End of Treatment (EOT) [62] | ||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. 'n'= Number analyzed= number of participants with data available for analysis at the given time point.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline and End of Treatment (Month 7)
|
||||||||||||||||||
| Notes [62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||||||||
|
|||||||||||||||||||
| Notes [63] - n=50,50 [64] - n=58,57 |
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||
End point title |
Phase 1: Percentage of Participants With Low and High ATA Titer Values [65] | ||||||||||||
End point description |
High and low ATA titer was defined for the ATA positive (transiently or persistently positive) participants only. High ATA titer was defined as participants who have at least one postbaseline ATA titer > 25. Low ATA titer was defined as participants whose postbaseline ATA titer are all <= 25. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Immunogenicity population included participants who received at least 1 dose of study drug and had the baseline immunogenicity sample and at least 1 postbaseline immunogenicity sample assessment. Immunogenicity population included participants who received at least 1 dose of study drug and had the baseline immunogenicity sample and at least 1 postbaseline immunogenicity sample assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 6 months
|
||||||||||||
| Notes [65] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||
End point title |
Phase 2: Percentage of Participants With Low and High ATA Titer Values [66] | ||||||||||||||||||
End point description |
High and low ATA titer was defined for the ATA positive (transiently or persistently positive) participants only. High ATA titer was defined as participants who have at least one postbaseline ATA titer >25. Low ATA titer was defined as participants whose postbaseline ATA titer are all <=25. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Immunogenicity population included participants who received at least 1 dose of study drug and had the baseline immunogenicity sample and at least 1 postbaseline immunogenicity sample assessment.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Up to 6 months
|
||||||||||||||||||
| Notes [66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||
End point title |
Phase 1 and 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ||||||||||||||||
End point description |
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. No sufficient number of participants with positive ATA status was available, thus the impact of ATA status on the pharmacokinetic parameters could not be assessed. Hence data is not available for this outcome measure.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Cycle 1 and 3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||||||
|
|||||||||||||||||
| Notes [67] - Data not available for this endpoint, no sufficient number of participants with positive ATA status. [68] - Data not available for this endpoint, no sufficient number of participants with positive ATA status. [69] - Data not available for this endpoint, no sufficient number of participants with positive ATA status. |
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Phase 1 and 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants | ||||||||||||||||
End point description |
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. No sufficient number of participants with positive ATA status was available, thus the impact of ATA status on the pharmacokinetic parameters could not be assessed. Hence data is not available for this outcome measure.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Cycle 1 and 3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||||||
|
|||||||||||||||||
| Notes [70] - Data not available for this endpoint, no sufficient number of participants with positive ATA status. [71] - Data not available for this endpoint, no sufficient number of participants with positive ATA status. [72] - Data not available for this endpoint, no sufficient number of participants with positive ATA status. |
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||
End point title |
Phase 1: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants [73] | ||||||||||||
End point description |
CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The data is reported per ATA status as categories. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Immunogenicity population included participants who received at least 1 dose of study drug and had the baseline immunogenicity sample and at least 1 postbaseline immunogenicity sample assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 24 months
|
||||||||||||
| Notes [73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||
End point title |
Phase 1: Number of ATA Positive and ATA Negative Participants With AEs and SAEs [74] | ||||||||||||||||
End point description |
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. The Safety Population included participants who received at least 1 dose of any drug in the A+AVD regimen, with data available for analyses.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to 24 months
|
||||||||||||||||
| Notes [74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 1 only. |
|||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||
End point title |
Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants [75] | ||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. No sufficient number of participants with positive ATA status was available, thus the impact of ATA status on the pharmacokinetic parameters could not be assessed. Hence data is not available for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||
| Notes [75] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||
|
|||||||||||||
| Notes [76] - Data not available for this endpoint, no sufficient number of participants with positive ATA status. [77] - Data not available for this endpoint, no sufficient number of participants with positive ATA status. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants [78] | ||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. No sufficient number of participants with positive ATA status was available, thus the impact of ATA status on the pharmacokinetic parameters could not be assessed. Hence data is not available for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
|
||||||||||||
| Notes [78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||
|
|||||||||||||
| Notes [79] - Data not available for this endpoint, no sufficient number of participants with positive ATA status. [80] - Data not available for this endpoint, no sufficient number of participants with positive ATA status. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||
End point title |
Phase 2: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants [81] | ||||||||||||||||||
End point description |
CR is defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Immunogenicity Population included participants who received at least 1 dose of study drug and had the baseline immunogenicity sample and at least 1 postbaseline immunogenicity sample assessment. 'n'= Number analyzed is the number of participants analyzed for the specified category.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Up to 24 months
|
||||||||||||||||||
| Notes [81] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||||||||
|
|||||||||||||||||||
| Notes [82] - n=48,3 [83] - n=55,4 |
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Phase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs [84] | ||||||||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. The Safety Population included participants who received at least 1 dose of any drug in the A+AVD regimen.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Up to 24 months
|
||||||||||||||||||||||||
| Notes [84] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||
End point title |
Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin M at the End of Treatment (EOT) [85] | ||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation, with data available for analyses. 'n' = Number analyzed is number of participants with data available for analysis at the given time point.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, EOT [Month 7]
|
||||||||||||||||||
| Notes [85] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||||||||
|
|||||||||||||||||||
| Notes [86] - n=48,46 [87] - n=56,53 |
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin A at EOT [88] | ||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Overall number analyzed are the participants with data available for analyses. 'n' = Number analyzed= number of participants with data available for analysis at the given time point.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, EOT [Month 7]
|
||||||||||||||||||
| Notes [88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||||||||
|
|||||||||||||||||||
| Notes [89] - n=48,47 [90] - n-57,54 |
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Phase 2: Immune Reconstitution-Change From Baseline in Tetanus at EOT [91] | ||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Overall number analyzed are the number of participants with data available for analyses. Number analyzed =number of participants with data available for analysis at the given time point.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, EOT [Month 7]
|
||||||||||||||||||
| Notes [91] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
|||||||||||||||||||
|
|||||||||||||||||||
| Notes [92] - n=48,42 [93] - n=56,49 |
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Phase 2: Immune Reconstitution-Change From Baseline in Haemophilus Influenzae B Antibody, IgG at EOT [94] | ||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Overall number analyzed are the number of participants with data available for analyses. Number analyzed= number of participants with data available for analysis at the given time point.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, EOT [Month 7]
|
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| Notes [94] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
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| Notes [95] - n=50,49 [96] - n=58,55 |
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| No statistical analyses for this end point | |||||||||||||||||||
|
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End point title |
Phase 2: Immune Reconstitution-Change From Baseline Poliovirus Antibodies at EOT [97] | ||||||||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Overall number analyzed are the number of participants with data available for analyses. 'n' = Number analyzed= number of participants with data available for analysis at the given time point.
|
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End point type |
Secondary
|
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End point timeframe |
Baseline, EOT [Month 7]
|
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| Notes [97] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
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| Notes [98] - n=50,50,50,50 [99] - n=58,56,58,56 |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Phase 2: Immune Reconstitution-Change From Baseline in Poliovirus Antibodies Ratio at EOT [100] | ||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Overall number analyzed are the number of participants with data available for analyses. 'n' = Number analyzed= number of participants with data available for analysis at the given time point.
|
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End point type |
Secondary
|
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End point timeframe |
Baseline, EOT [Month 7]
|
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| Notes [100] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
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| Notes [101] - n=48,46 [102] - n=56,56 |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Phase 2: Immune Reconstitution-Change From Baseline in Peripheral Blood CD34+A at EOT [103] | ||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Overall number analyzed are the number of participants with data available for analyses. 'n' = Number analyzed= number of participants with data available for analysis at the given time point.
|
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End point type |
Secondary
|
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End point timeframe |
Baseline, EOT [Month 7]
|
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| Notes [103] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
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| Notes [104] - n=38,29 [105] - n=44,34 |
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| No statistical analyses for this end point | |||||||||||||||||||
|
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End point title |
Phase 2: Immune Reconstitution-Change From Baseline in Total Lymphocyte Count at EOT [106] | ||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation.
|
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End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, EOT [Month 7]
|
||||||||||||||||||
| Notes [106] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
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| Notes [107] - n=49,48 [108] - n=57,56 |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) and CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT [109] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2. Immune Reconstitution Population included participants who received at least 1 dose of study drug and had a sufficient immune reconstitution blood sampling to allow for immune reconstitution evaluation. Overall number analyzed are the number of participants with data available for analyses. 'n' = Number analyzed= number of participants with data available for analysis at the given time point.
|
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End point type |
Secondary
|
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End point timeframe |
Baseline, EOT [Month 7]
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [109] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be reported in Phase 2 only. |
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| Notes [110] - n=39,29,29,23,39,29,39,29,39,29,35,26,39,29,39,29 [111] - n=32,23,32,29, 32,23,32, 23,32, 23, 28,20,32,23,32,23 |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From first dose of study drug up to 30 days post last dose (Up to approximately 4 years)
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Adverse event reporting additional description |
The Safety Population included participants who received at least 1 dose of any drug in the A+AVD regimen. Data is reported in 2 arms: Phase 1 includes participants who received at least one dose of study drug in Phase 1 and continued to Phase 2 to receive the same drug; Phase 2 included participants who were enrolled directly in Phase 2.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
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Reporting groups
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Reporting group title |
Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD
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Reporting group description |
Brentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD
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Reporting group description |
Brentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles. Participants who received at least one dose of study in Phase 1 and continued to receive the study drug in Phase 2 were included in this arm group. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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10 Dec 2019 |
The following changes were implemented as per Amendment 3: 1. Optional long-term follow-up procedures are added 2. Protocol signatory updates 3. Adjusted the total number of participating sites. |
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11 Jun 2021 |
The following changes were implemented as per Amendment 4: 1. Modifications in study conduct instituted in response to the COVID-19 pandemic. 2. Clarification of time points for analysis and reporting of study results. 3. Additional guidance pertaining to the long-term follow-up procedures. 4. Updated sponsor name. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
